Patterns in protein flexibility: a comparison of NMR "ensembles", MD trajectories and crystallographic B-factors

Abstract

Proteins are molecular machines requiring flexibility to function. Crystallographic B-factors and Molecular Dynamics (MD) simulations both provide insights into protein flexibility on an atomic scale. Nuclear Magnetic Resonance (NMR) lacks a universally accepted analog of the B-factor, however, a lack of convergence in atomic coordinates in an NMR-based structure calculation also suggests atomic mobility. This paper describes a pattern in the coordinate uncertainties of backbone heavy atoms in NMR-derived structural \"ensembles\" first noted in the development of FindCore2 (previously called Expanded FindCore: DA Snyder, J Grullon, YJ Huang, R Tejero, GT Montelione, Proteins: Structure, Function, and Bioinformatics 82 (S2), 219-230) and demonstrates that this pattern exists in coordinate variances across MD trajectories but not in crystallographic B-factors. This either suggests that MD trajectories and NMR \"ensembles\" capture motional behavior of peptide bond units not captured by B-factors or indicates a deficiency common to force fields used in both NMR and MD calculations. Additionally, a comparison of C B-factors with C coordinate variability in NMR \"ensembles\" and MD trajectories shows that NMR-derived coordinate uncertainties measure variability in atomic positions as well as crystallographic B-factors and superimpositions of MD trajectories do.